BACKGROUND: Endovascular recanalization in patients with chronic CAO has been reported to be feasible, but technically challenging.
METHODS: Endovascular attempts in 138 consecutive chronic CAO patients with impaired ipsilateral hemisphere perfusion were reviewed. We analyzed potential variables including epidemiology, symptomatology, angiographic morphology, and interventional techniques in relation to the technical success.
RESULTS: The technical success rate was 61.6%. Multivariate analysis showed absence of prior neurologic event (odds ratio [OR]: 0.27; 95% confidence interval [CI]: 0.10 to 0.76), nontapered stump (OR: 0.18; 95% CI: 0.05 to 0.67), distal internal carotid artery (ICA) reconstitution via contralateral injection (OR: 0.19; 95% CI: 0.05 to 0.75), and distal ICA reconstitution at communicating or ophthalmic segments (OR:0.12; 95% CI: 0.04 to 0.36) to be independent factors associated with lower technical success. Point scores were assigned proportional to model coefficients, and technical success rates were >80% and <40% in patients with scores of ≤1 and ≥4, respectively. The c-indexes for this score system in predicting technical success was 0.820 (95% CI: 0.748 to 0.892; p < 0.001) with a sensitivity of 84.7% and a specificity of 67.9%.
CONCLUSIONS: Absence of prior neurologic event, nontapered stump, distal ICA reconstitution via contralateral injection, and distal ICA reconstitution at communicating or ophthalmic segments were identified as independent negative predictors for technical success in endovascular recanalization for CAO.
PURPOSE: To evaluate the feasibility of percutaneous posterolateral fusion in the spine utilizing rhBMP-2.
STUDY DESIGN: Animal study.
METHODS: This is an animal research model involving 32 New Zealand white rabbits stratified into 4 study groups: control, autogenous iliac crest bone graft (ICBG), demineralized bone matrix (DBM), and rhBMP-2 groups, with 8 study subjects per group. The rhBMP-2 group was subdivided into the open technique (right side) and the percutaneous technique groups (left side). Fusion was graded at 6 weeks and 3 months after plain radiography, computed tomography, and clinical assessment with the following grading system: grade A, no bone formation; grade B, non-bridging bone formation; grade C, fusion; and grade D, fusion with ectopic bone formation.
RESULTS: No fusion was noted in the placebo and the DBM groups. However, in the DBM group, bone formation occurred in 37.5% of the subjects. The rhBMP-2 group had a higher fusion rate compared with the ICBG group at 6 weeks and 3 months. The fusion rate for the ICBG, the rhBMP-2 (open), and the rhBMP-2 (percutaneous) groups were 37.5%, 87.5%, and 50.0% at 6 weeks and 50.0%, 100.0%, and 62.5% at 3 months, respectively. Ectopic bone formation occurred in 12.5% of the cases in the rhBMP-2 (percutaneous) group and in 25.0% of the cases in the rhBMP-2 (open) group.
CONCLUSIONS: Usage of rhBMP-2 is feasible for percutaneous posterolateral fusion of the lumbar spine in this animal model. However, a more precise delivery system might improve the fusion rate when the percutaneous technique is used. A significant rate of ectopic bone formation occurred when rhBMP-2 was used.
PURPOSE: To develop 3D personalized left ventricular (LV) models and thickening assessment framework for assessing regional wall thickening dysfunction and dyssynchrony in AMI patients.
STUDY TYPE: Retrospective study, diagnostic accuracy.
SUBJECTS: Forty-four subjects consisting of 15 healthy subjects and 29 AMI patients.
FIELD STRENGTH/SEQUENCE: 1.5T/steady-state free precession cine MRI scans; LGE MRI scans.
ASSESSMENT: Quantitative thickening measurements across all cardiac phases were correlated and validated against clinical evaluation of infarct transmurality by an experienced cardiac radiologist based on the American Heart Association (AHA) 17-segment model.
STATISTICAL TEST: Nonparametric 2-k related sample-based Kruskal-Wallis test; Mann-Whitney U-test; Pearson's correlation coefficient.
RESULTS: Healthy LV wall segments undergo significant wall thickening (P 50% transmurality) underwent remarkable wall thinning during contraction (thickening index [TI] = 1.46 ± 0.26 mm) as opposed to healthy myocardium (TI = 4.01 ± 1.04 mm). For AMI patients, LV that showed signs of thinning were found to be associated with a significantly higher percentage of dyssynchrony as compared with healthy subjects (dyssynchrony index [DI] = 15.0 ± 5.0% vs. 7.5 ± 2.0%, P
METHODS: We developed mouse models representing three different phenotypes of allergic airway inflammation-eosinophilic, mixed, and neutrophilic asthma via different methods of house dust mite sensitization and challenge. Transcriptomic analysis of the lungs, followed by the RT-PCR, western blot, and confocal microscopy, was performed. Primary human bronchial epithelial cells cultured in air-liquid interface were used to study the mechanisms revealed in the in vivo models.
RESULTS: By whole-genome transcriptome profiling of the lung, we found that airway tight junction (TJ), mucin, and inflammasome-related genes are differentially expressed in these distinct phenotypes. Further analysis of proteins from these families revealed that Zo-1 and Cldn18 were downregulated in all phenotypes, while increased Cldn4 expression was characteristic for neutrophilic airway inflammation. Mucins Clca1 (Gob5) and Muc5ac were upregulated in eosinophilic and even more in neutrophilic phenotype. Increased expression of inflammasome-related molecules such as Nlrp3, Nlrc4, Casp-1, and IL-1β was characteristic for neutrophilic asthma. In addition, we showed that inflammasome/Th17/neutrophilic axis cytokine-IL-1β-may transiently impair epithelial barrier function, while IL-1β and IL-17 increase mucin expressions in primary human bronchial epithelial cells.
CONCLUSION: Our findings suggest that differential expression of TJ, mucin, and inflammasome-related molecules in distinct inflammatory phenotypes of asthma may be linked to pathophysiology and might reflect the differences observed in the clinic.
MATERIALS AND METHODS: We searched candidate genes from the schizophrenia database and performed a comprehensive meta-analysis using all the available data up to August 2017. The association between susceptible SNPs and schizophrenia was assessed by the pooled odds ratio with 95% confidence interval using fixed-effect and random-effect models.
RESULTS: A total of 21 studies including 8291 cases and 9638 controls were used for meta-analysis. Three investigated SNPs were rs165599, rs3737597, and rs1047631 of COMT, DISC1, and DTNBP1, respectively. Our results suggested that rs3737597 showed a significant association with schizophrenia in Europeans (odds ratio: 1.584, P: 0.002, 95% confidence interval: 1.176-2.134) under a random-effect framework.
CONCLUSION: This meta-analysis indicated that rs3737597 of DISC1 was significantly associated with schizophrenia in Europeans, and it can be suggested as an ethnic-specific risk genetic factor.
OBJECTIVE: To determine and compare the clinical phenotype and organ damage between male and female patients with SLE in Malaysia.
METHODOLOGY: This was a cross-sectional study involving SLE patients from Universiti Kebangsaan Malaysia Medical Centre from June 2016 until June 2017. Information on their socio-demographics and disease characteristics were obtained from the clinical records. Disease damage was assessed using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) damage index (SDI) scores. The disease characteristics, autoantibody profiles and organ damage were compared between male and female patients, and multivariable analysis using male sex as dependent variable was then performed.
RESULTS: A total of 418 patients were recruited and a total of 59 (14.1%) patients were male. Male patients presented with lower SLE ACR criteria at initial presentation but a significantly higher number of them had renal involvement (lupus nephritis) (78.0% versus 63.8%, p = 0.04). Male patients had less musculoskeletal involvement (45.8% versus 63.0%, p = 0.02) and tended to have lesser mucocutaneous involvement. Immunologic profile revealed that a lower number of male patients had positive anti-Ro antibody (22.7% versus 44.7%, p = 0.04) and they tended to have positive lupus anticoagulant antibody (27.6% versus 14.3%, p = 0.06). Presence of organ damage (SDI score ≥ 1) was significantly higher among males (55.9% versus 39.6%, p = 0.02) with higher renal damage (25.4% versus 9.2%, p = 0.004) and cardiovascular event of ischaemic heart disease or stroke (20.3% versus 7.0%, p = 0.004). They were also inclined to develop damage much earlier as compared to female patients, 3 (interquartile range (IQR) 7.5) versus 5 (IQR 7) years, p = 0.08. The occurrence of disease damage was independently associated with male gender with odds ratio of 1.9 (95% confidence interval 1.1-3.5), p = 0.02.
CONCLUSION: Male patients with SLE have more severe disease with renal damage and cardiovascular event.
METHODS: The dengue infection in mouse model was established by inoculation of non-mouse adapted New Guinea C strain dengue virus (DEN-2) in AG129 mice. The freeze-dried CPLJ compounds were identified by Ultra-High Performance Liquid Chromatography High Resolution Accurate Mass Spectrometry analysis. The infected AG129 mice were orally treated with 500 mg/kg/day and 1000 mg/kg/day of freeze-dried CPLJ, starting on day 1 post infection for 3 consecutive days. The blood samples were collected from submandibular vein for plasma NS1 assay and quantitation of viral RNA level by quantitative reverse transcription PCR.
RESULTS: The AG129 mice infected with dengue virus showed marked increase in the production of plasma NS1, which was detectable on day 1 post infection, peaked on day 3 post-infection and started to decline from day 5 post infection. The infection also caused splenomegaly. Twenty-four compounds were identified in the freeze-dried CPLJ. Oral treatment with 500 mg/kg/day and 1000 mg/kg/day of freeze-dried CPLJ did not affect the plasma NS1 and dengue viral RNA levels. However, the morbidity level of infected AG129 mice were slightly decreased when treated with freeze-dried CPLJ.
CONCLUSION: Oral treatment of 500 mg/kg/day and 1000 mg/kg/day of freeze-dried CPLJ at the onset of viremia did not affect the plasma NS1 and viral RNA levels in AG129 mice infected with non-mouse adapted New Guinea C strain dengue virus.
DESIGN: This is a retrospective analysis of women with ST-elevation MI (STEMI) and non-STEMI (NSTEMI) from 18 hospitals across Malaysia using the Malaysian National Cardiovascular Database registry-acute coronary syndrome (NCVD-ACS).
PARTICIPANTS: Women patients diagnosed with acute MI from year 2006 to 2013 were identified and divided into young (age ≤ 45, n=292) and older women (age >45, n=5580).
PRIMARY OUTCOME MEASURE: Comparison of demographics, clinical characteristics and in-hospital management was performed between young and older women. In-hospital and 30-day all-cause mortality were examined.
RESULTS: Young women (mean age 39±4.68) made up 5% of women with MI and were predominantly of Malay ethnicities (53.8%). They have a higher tendency to present as STEMI compared with older women. Young women have significantly higher rates of family history of premature coronary artery disease (CAD) (20.5% vs 7.8% p<0.0001). The prevalence of risk factors, such as hypertension, diabetes and dyslipidaemia was high in both groups. The primary reperfusion strategy was thrombolysis with no significant differences observed in the choice of intervention for both groups. Other than aspirin, rates of prescriptions for evidence-based medications were similar with >80% prescribed statins and aspirin. The all-cause mortality rates of young women were lower for both in-hospital and 30 days, especially in those with STEMI with adjusted mortality ratio to the older group, was 1:9.84.
CONCLUSION: Young women with MI were over-represented by Malays and those with a family history of premature CAD. Preventive measures are needed to reduce cardiovascular risks in young women. Although in-hospital management was similar, short-term mortality outcomes favoured young compared with older women.
METHODS: This study was performed using data from a large multinational prospective cohort. Active lupus nephritis at any visit was defined by the presence of urinary casts, proteinuria, haematuria or pyuria, as indicated by the cut-offs in the SLE Disease Activity Index (SLEDAI)-2K, collected at each visit. Organ damage accrual was defined as a change of SLICC-ACR Damage Index (SDI) score >0 units between baseline and final annual visits. Renal damage accrual was defined if there was new damage recorded in renal SDI domains (estimated glomerular filtration rate <50%/proteinuria >3.5 g per 24 h/end-stage kidney disease). Time-dependent hazard regression analyses were used to examine the associations between active lupus nephritis and damage accrual.
RESULTS: Patients (N = 1735) were studied during 12,717 visits for a median (inter-quartile range) follow-up period of 795 (532, 1087) days. Forty per cent of patients had evidence of active lupus nephritis at least once during the study period, and active lupus nephritis was observed in 3030 (24%) visits. Forty-eight per cent of patients had organ damage at baseline and 14% accrued organ damage. Patients with active lupus nephritis were 52% more likely to accrue any organ damage compared with those without active lupus nephritis (adjusted hazard ratio = 1.52 (95% confidence interval (CI): 1.16, 1.97), p
METHODS: The AG129 mice were fed orally with FCPLJ for 3 consecutive days after 24 h of dengue virus inoculation. Plasma cytokines were screened by using ProcartaPlex immunoassay. The gene expression in the liver was analyzed by using RT2 Profiler PCR Array.
RESULTS: The results showed that FCPLJ treatment has increased the plasma CCL2/MCP-1 level during peak of viremia. Gene expression study has identified 8 inflammatory cytokine genes which were downregulated in the liver of infected AG129 mice treated with FCPLJ. The downregulated inflammatory cytokine genes were CCL6/MRP-1, CCL8/MCP-2, CCL12/MCP-5, CCL17/TARC, IL1R1, IL1RN/IL1Ra, NAMPT/PBEF1 and PF4/CXCL4.
CONCLUSION: The findings indicated the possible immunomodulatory role of FCPLJ during dengue virus infection in AG129 mice.